5-Fluoro-2-hydroxypyridine

5-Fluoro-2-hydroxypyridine is a halogenated compound used in the synthesis of 5-Fluoro-2-hydroxy-3-nitropyridine and 5-halogenated pyrimidine compounds.

5-Fluoro-2-hydroxypyridine is synthesised using 5-fluoro-2-methoxypyridine as a raw material by chemical reaction. The specific synthesis steps are as follows:
A total of 4.6 L of toluene solution containing 3-80 was placed in several sealed tubes and treated with 900 ml of 35percent HCl at 145° C. for 2 hr. LC/MS showed no starting material, only 4. The toluene solution was decanted and discarded. The aqueous phase was washed with EtOAc and concentrated down to remove volatiles to afford a brown solid containing the desired fluoro-hydroxypyridine 4-80. [1488] A total of 244 g of this solid was collected and taken to next step as is (it was not completely dry). [1489] Note: We have subsequently run this by decanting the toluene layer first prior to heating to reduce volumes. Same reaction was carried out using HBr (48percent in H2O) at 100° C. for 6 h with similar result to the literature procedure 49percent yield. [1490] Ref: J. Heterocyclic Chem., 10, 779, 1973 (for above Reactions, Including Analytical Data).

[1] Patent: US2004/110785, 2004, A1. Location in patent: Page 211
[2] Patent: US2006/142298, 2006, A1. Location in patent: Page/Page column 13
[3] Patent: US2005/209246, 2005, A1. Location in patent: Page/Page column 30; 31
[4] Patent: US2006/142298, 2006, A1. Location in patent: Page/Page column 11; 13